Abnormal keratinocyte differentiation in the nasal planum of Labrador Retrievers with hereditary nasal parakeratosis (HNPK).

Autor: Bannoehr J; Division of Clinical Dermatology, Department of Clinical Veterinary Science, Vetsuisse Faculty, University of Bern, Bern, Switzerland.; DermFocus, Vetsuisse Faculty, University of Bern, Bern, Switzerland., Balmer P; Division of Clinical Dermatology, Department of Clinical Veterinary Science, Vetsuisse Faculty, University of Bern, Bern, Switzerland.; DermFocus, Vetsuisse Faculty, University of Bern, Bern, Switzerland., Stoffel MH; Division of Veterinary Anatomy, Vetsuisse Faculty, University of Bern, Bern, Switzerland., Jagannathan V; Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland., Gaschen V; Division of Veterinary Anatomy, Vetsuisse Faculty, University of Bern, Bern, Switzerland., Kühni K; Division of Veterinary Anatomy, Vetsuisse Faculty, University of Bern, Bern, Switzerland., Sayar B; DermFocus, Vetsuisse Faculty, University of Bern, Bern, Switzerland.; Department of Clinical Research, Molecular Dermatology and Stem Cell Research, University of Bern, Bern, Switzerland., Drögemüller M; Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland., Howald D; Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland., Wiener DJ; DermFocus, Vetsuisse Faculty, University of Bern, Bern, Switzerland.; Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland., Leeb T; DermFocus, Vetsuisse Faculty, University of Bern, Bern, Switzerland.; Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland., Welle MM; DermFocus, Vetsuisse Faculty, University of Bern, Bern, Switzerland.; Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland., Müller EJ; DermFocus, Vetsuisse Faculty, University of Bern, Bern, Switzerland.; Department of Clinical Research, Molecular Dermatology and Stem Cell Research, University of Bern, Bern, Switzerland.; Clinic for Dermatology, Inselspital, Bern University Hospital, Bern, Switzerland., Roosje PJ; Division of Clinical Dermatology, Department of Clinical Veterinary Science, Vetsuisse Faculty, University of Bern, Bern, Switzerland.; DermFocus, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2020 Mar 02; Vol. 15 (3), pp. e0225901. Date of Electronic Publication: 2020 Mar 02 (Print Publication: 2020).
DOI: 10.1371/journal.pone.0225901
Abstrakt: Hereditary nasal parakeratosis (HNPK) is an inherited disorder described in Labrador Retrievers and Greyhounds. It has been associated with breed-specific variants in the SUV39H2 gene encoding a histone 3 methyltransferase involved in epigenetic silencing. Formalin-fixed biopsies of the nasal planum of Labrador Retrievers were screened by immunofluorescence microscopy for the presence and distribution of epidermal proliferation and differentiation markers. Gene expression of these markers was further analysed using RNA sequencing (RNA-seq) and ultrastructural epidermal differences were investigated by electron microscopy. Differentiation of the nasal planum in the basal and suprabasal epidermal layers of HNPK-affected dogs (n = 6) was similar compared to control dogs (n = 6). In the upper epidermal layers, clear modifications were noticed. Loricrin protein was absent in HNPK-affected nasal planum sections in contrast to sections of the same location of control dogs. However, loricrin was present in the epidermis of paw pads and abdominal skin from HNPK dogs and healthy control dogs. The patterns of keratins K1, K10 and K14, were not markedly altered in the nasal planum of HNPK-affected dogs while the expression of the terminal differentiation marker involucrin appeared less regular. Based on RNA-seq, LOR and IVL expression levels were significantly decreased, while KRT1, KRT10 and KRT14 levels were up-regulated (log2fold-changes of 2.67, 3.19 and 1.71, respectively) in HNPK-affected nasal planum (n = 3) compared to control dogs (n = 3). Electron microscopical analysis revealed structural alterations in keratinocytes and stratum corneum, and disrupted keratinocyte adhesions and distended intercellular spaces in lesional samples (n = 3) compared to a sample of a healthy control dog (n = 1). Our findings demonstrate aberrant keratinocyte terminal differentiation of the nasal planum of HNPK-affected Labrador Retrievers and provide insights into biological consequences of this inactive SUV39H2 gene variant.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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